It is our primary goal to combine the cellular, molecular, and radiochemical capabilities of our laboratories in order to elucidate the specific deoxynucleoside-hydrocarbons responsible for the biological (cytotoxic, mutagenic, carcinogenic) effects of 7, 12 - dimethylbenz(a) anthracene (DMBA) and selected DMBA derivatives. Utilizing 14C labeled DMBA and related derivatives of high specific activity (synthesized in our laboratories) we will compare the DN-HC profile of each of these compounds with one another. The differential rate of removal of the various DN-HC compounds will be determined and compared with their respective biological effects. Non-label derivatives will be utilized to access the ability of these compounds to induced DNA damage (as measured by unscheduled DNA synthesis, BUdR photolysis and alkaline sucrose sedimentation). We will further utilize selected repair deficient mutants human fibroblast cell cultures in order to characterize these mutants and the forms of repair involved in removal of DMBA induced DNA damage. Based upon the assumption that rapidly removed DN-HC(s) compound(s) have no biological effect, we will characterize the chemical nature of not only removed DN-HC(s) but also those not removed by DNA repair processes prior to DNA replication. In order to perform these studies it is necessary that we be able to detect one molecule in 20,000 and for these reasons it is of major importance that radiolabeled DMBA (14C) of high specific activity (described in this proposal) be employed. Only because of the excellent working relationship between chemical and biological groups within this project is it possible to accomplish the specific aims of this proposal.